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This systematic review examines the relationship between neurofibromatosis type 1 (NF1), juvenile xanthogranulomas (JXG), and juvenile myelomonocytic leukemia (JMML). The study reveals that JMML is more prevalent in NF1 patients with JXG compared to those without. Patients with NF1, JXG, and JMML tend to be younger at diagnosis, have earlier detection of JXG, and have larger JXG compared to other groups. The study also finds that leukaemic cells in patients with JMML show evidence of biallelic inactivation of NF1. The article suggests that increased monitoring for JMML may be necessary in NF1 patients with certain risk factors, such as a positive family history of NF1, male gender, and early onset and larger size of JXG. [Extracted from the article]

B Introduction: b AZD4573, a potent and highly selective CDK9i, rapidly induces apoptosis in human haematologic cancer cell lines. PHASE 1B/2A STUDY OF AZD4573 (CDK9I) AND ACALABRUTINIB IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (R/R DLBCL) In a first-in-human trial, AZD4573 monotherapy had manageable safety in pts with I r/r i haematologic cancers and antitumour activity in those with DLBCL. [Extracted from the article]

Based on 2D seismic profiles, multibeam and seabed grab cores acquired during the Garanti cruise in 2017, 1–5 km wide seabed giant polygons were identified in the Grenada basin, covering a total area of ∼55,000 km2, which is the largest area of outcropping polygonal faults (PF) ever found on Earth so far. They represent the top part of an active 700–1,200 m thick underlying polygonal fault system (PFS) formed due to the volumetric contraction of clay‐ and smectite‐rich sediments, initiated in the sub‐surface at the transition between the Early to Middle Pliocene. The short axes of the best‐fit ellipses obtained from a graphical center‐to‐center method were interpreted as the local orientation of a preferential contraction perpendicular to the creep deformation of slope sediments. In the North Grenada Basin, the polygons are relatively regular, but their short axes seem to be parallel to a N40°E extension recently evidenced in the forearc, possibly extending in the backarc, but not shown in the study area. They are most probably related to a progressive burial due to a homogeneous subsidence. In the South Grenada Basin, the polygons are more elongated and their axes are progressively rotating southeastward toward the depocenter, indicating a creep deformation toward the center of the basin created by a differential subsidence. Seabed polygons and underlying PF could thus be indicative of the deformation regime of shallow sediments related to main slopes controlled by two different basin architectures. Key Points: Seabed giant polygons in the Grenada Basin cover the largest area (55,000 km2) ever found on EarthThe short axis of best‐fit ellipses of polygons may represent the orientation of the creep deformation of slope sedimentsThe north and south tectonic domains in the Grenada Basin are marked by major differences in the shape and orientation of seabed polygons [ABSTRACT FROM AUTHOR]

The diversity of primary producers strongly affects the structure and diversity of species assemblages at other trophic levels. However, limited knowledge exists of how plant diversity effects at small spatial scales propagate to consumer communities at larger spatial scales. We assessed arthropod community β and γ‐diversity in response to experimentally manipulated plant community richness in two long‐term grassland biodiversity experiments (Jena, Germany and Cedar Creek, USA) replicated over two years. We calculated arthropod species turnover among all plot combinations (β‐diversity), and accumulated number of arthropod species occurring on (1) all pairwise plot combinations and (2) 40 randomly selected six‐plot combinations (γ‐diversity). The components of arthropod diversity were tested against two measures of plant diversity, namely average plant α‐diversity (PSR¯) and the average difference in plant α‐diversity between plots (ΔPSR). Whereas PSR¯ points to the overall importance of plant α‐diversity for arthropod community turnover and diversity on a larger scale, ΔPSR represents the role of habitat heterogeneity. We demonstrate that arthropod γ‐diversity is supported by high, homogeneous plant α‐diversity, despite lower arthropod β‐diversity among high‐ compared to low‐diversity plant communities. We also show that, in six‐plot combinations, average plant α‐diversity has a positive influence on arthropod γ‐diversity only when homogeneity in plant α‐diversity is also high. Varying heterogeneity in six‐plot combinations showed that combinations consisting solely of plots with an intermediate level of plant α‐diversity support a higher number of arthropod species compared to combinations that contain a mix of high‐ and low‐diversity plots. In fact, equal levels of arthropod diversity were found for six‐plot combinations with only intermediate or high plant α‐diversity, due to saturating benefits of local and larger‐scale plant diversity for higher trophic levels. Our results, alongside those of recent observational studies, strongly suggest that maintaining high α‐diversity in plant communities is important for conserving multiple components of arthropod diversity. As arthropods carry out a range of essential ecosystem functions, such as pollination and natural pest‐control, our findings provide crucial insight for effective planning of human‐dominated landscapes to maximize both ecological and economic benefits in grassland systems. [ABSTRACT FROM AUTHOR]

Mating strategies contributing to a balance between inbreeding and outcrossing are understudied in all but a few model fungal pathogens. This study examined factors that influence the occurrence of the sexual state of Pyrenophora semeniperda. It was consistently found to have functional copies of the MAT1‐1 and MAT1‐2 idiomorphs essential for sexual reproduction, despite considerable polymorphism in both single nucleotide polymorphisms (SNPs) and number of 18‐base minisatellite repeats. The two idiomorphs occurred at approximately equal frequencies across 25 populations on Bromus tectorum seeds in the western United States, suggesting maintenance of sexual reproduction. The putative mating system is described as facultative pseudohomothallism, with only one of the two MAT1 idiomorphs found in a nucleus. Unikaryotic strains of opposite mating type can potentially mate, as can nuclei of opposite mating type in a thallus that results from anastomosis between vegetatively compatible unikaryotic strains. Strains shown to be dikaryotic using simple sequence repeat (SSR) markers may contain either or both MAT1 idiomorphs. Most populations consist of a mixture of MAT1‐1,MAT1‐2 and MAT1‐1/MAT1‐2 genotypes. A possible constraint on recombination is the presence of multiple strain groups characterized by ITS haplotype. These are apparently vegetatively incompatible, as even dikaryotic strains are invariably composed of a single ITS haplotype. Different ITS haplotypes also have unique combinations of MAT1‐1 and MAT1‐2 allelic variants, suggesting that perhaps these strain groups are also sexually incompatible. Phylogenetic analysis using both genome‐wide SNP/indel polymorphisms and SSR markers demonstrated genetic divergence among ITS haplotypes, supporting the hypothesis that these strain groups may represent cryptic species. [ABSTRACT FROM AUTHOR]

Roman‐period mummy portraits are considered to be ancient antecedents of modern portraiture. However, the techniques and materials used in their manufacture are not thoroughly understood. Analytical study of the pigments as well as the binding materials helps to address questions on what aspects of the painting practices originate from Pharaonic and/or Graeco‐Roman traditions, and can aid in determining the provenance of the raw materials from potential locations across the ancient Mediterranean and European worlds. Here, one of the largest assemblages of mummy portraits to remain intact since their excavation from the site of Tebtunis in Egypt was examined using multiple analytical techniques to address how they were made. The archaeological evidence suggests that these portraits were products of a single workshop and, correspondingly, they are found to be made using similar techniques and materials: wax‐based and lead white–rich paint combined with a variety of iron‐based pigments (including hematite, goethite and jarosite), as well as Egyptian blue, minium, indigo and madder lake to create subtle variations and tones. [ABSTRACT FROM AUTHOR]

Background and Objectives: A lateral flow assay for simultaneous blood group typing of ABO, RhD, C, E, c, e, Cw and K with stable end‐point and without centrifugation is in routine use since several years (MDmulticard®). The typing of extended phenotype parameters belonging to the Duffy, Kidd, MNSs blood group systems and others, however, has not yet been demonstrated for this technique. Reliable detection of Fyx, a weak Fyb phenotype with a pronounced quantitative reduction of the number of Fyb antigens on the erythrocyte surface, remains a weakness of current serological blood grouping techniques. Material and Methods: The performance characteristics of the following reagents were evaluated in donor and patient samples in lateral flow technology (MDmulticard®): Anti‐Fya, ‐Fyb, ‐Jka, ‐Jkb, ‐S, ‐s̅, ‐P1 and ‐k. The sensitivity to detect Fyx was in addition evaluated with Fyx positive samples, which had been preselected by MALDI‐TOF MS‐based genotyping. Results: All results obtained with the MDmulticard® were in full accordance with those of the CE‐certified reference products for all the eight reagent formulations used: Anti‐Fya, ‐Fyb, ‐Jka, ‐Jkb, ‐S, ‐s̅, ‐P1 and –k. Also, all Fyx phenotypes of the selected population of 93 positive samples, originally identified by MALDI‐TOF MS‐based genotyping, were reliably detected by the lateral flow assay. Conclusion: Extended phenotype blood group parameters, including the serologically challenging Fyx phenotype, can be determined simultaneously, rapidly and accurately using the lateral flow (MDmulticard®) technology, even in cases when IgG class antibodies are the only source of diagnostic antibodies. [ABSTRACT FROM AUTHOR]

Activated Tregs were enriched in NHL tumors and had higher expression of checkpoint receptors (TNFRSF4, TNFRSF18, TIGIT), NF- B pathway (NFKBIA, NFKBIZ, REL), chemokine receptors (CXCR4) and transcription factors (JUN, JUNB, BATF) compared to resting Tregs. B Introduction: b Tumor-infiltrating regulatory T cells (Tregs) contribute to an immunosuppressive tumor microenvironment. B Conclusion: b This study demonstrates that Tregs infiltrating NHL tumors are transcriptionally and functionally diverse and include highly immunosuppressive activated Tregs co-expressing several checkpoint receptors, which distinguish them from resting Tregs. [Extracted from the article]

Zoonotic Salmonella infections cause approximately 130 000 illnesses annually in the United States. Of 72.9 million US households owning at least one pet, five million own small mammals; 3000 hedgehogs were documented by USDA in USDA-licensed breeding facilities and pet stores in 2012. State health department collaborators and PulseNet, the national bacterial subtyping network, identified human infections of a Salmonella Typhimurium outbreak strain, which were investigated by CDC, USDA- APHIS and state public and animal health officials. A case was defined as an illness in a person infected with the outbreak strain identified between 1 December 2011 and 3 June 2013. Investigators collected information on patient exposures, cultured animal and environmental specimens for Salmonella, and conducted traceback investigations of USDA-licensed hedgehog facilities. There were 26 cases in 12 states. Illness onset dates ranged from 26 December 2011 to 8 April 2013. The median patient age was 15 years (range = <1-91 years); 58% were female. Among 23 persons with available information, 8 (35%) were hospitalized and one outbreak strain -associated death was reported. Of 25 patients with available information, 20 (80%) reported pet hedgehog contact in the week before illness onset. The outbreak strain was isolated from animal and environmental samples collected from three ill persons' homes in three states. Hedgehogs were purchased in geographically distant states from USDA-licensed breeders (10/17, 59%); a USDA-licensed pet store (1/17, 6%); unlicensed or unknown status breeders (3/17, 18%); and private individuals (3/17, 18%). Traceback investigations of USDA-licensed facilities did not reveal a single source of infection. Public and animal health collaboration linked pet hedgehog contact to human infections of Salmonella Typhimurium, highlighting the importance of a One Health investigative approach to zoonotic salmonellosis outbreaks. More efforts are needed to increase awareness among multiple stakeholders on the risk of illness associated with pet hedgehogs. [ABSTRACT FROM AUTHOR]

Aim To evaluate the antimicrobial effect of laser-activated irrigation ( LAI) on biofilms formed in simulated root canals. Methodology A dual-species biofilm of Enterococcus faecalis and Streptococcus mutans was grown in a resin root canal model. Biofilms were formed over 48 h and subsequently subjected to the following treatments, all executed for 20 s: syringe irrigation ( SI) with a 27G needle, ultrasonically activated irrigation ( UAI) with a size 20 Irrisafe file, and LAI with a 2940 nm Er: YAG laser (20 Hz, 50 μs, 20 or 40 mJ, conical fibre tip at two positions). Tests were performed with both sterile saline as well as Na OCl (2.5%) as the irrigant. Surviving bacteria were harvested and the number of CFU was determined by plate counting and compared across groups ( anova, P ≤ 0.05). Results Using saline as the irrigant, significant reductions in viable counts compared to untreated controls were observed for ultrasonically activated irrigation (0.52 log10 reduction) and for all laser-activated irrigation groups (>1 log10 reduction), but not for syringe irrigation (<0.25 log10 reduction). The reductions in the laser-activated irrigation groups were significantly greater than those of ultrasonically activated irrigation. With Na OCl as the irrigant, significant reductions (>2.2 log10 units) in the number of attached bacteria were observed for all treatment groups with no significant differences between laser-activated and ultrasonically activated irrigation. Conclusions Within the limitations of this in vitro set-up, laser-activated irrigation removed more biofilm than ultrasonically activated irrigation when using saline as the irrigant, indicating greater physical biofilm removal. The use of Na OCl resulted in greater biofilm reduction with no significant differences between treatment groups. [ABSTRACT FROM AUTHOR]

Simeprevir is a hepatitis C virus NS3/4A protease inhibitor. Hepatitis C virus baseline NS3/4A polymorphisms and emerging mutations were characterized in treatment-naїve and treatment-experienced genotype 4-infected patients treated with simeprevir+peginterferon/ribavirin in the RESTORE study. Population sequencing of the NS3/4A region was performed and in vitro simeprevir activity against site-directed mutants or chimeric replicons with patient-derived NS3 protease sequences was assessed in a transient replicon assay. Simeprevir remained active against most (83/91 [91%]) baseline isolates tested in the chimeric replicon assay. Eight baseline isolates reduced simeprevir activity; these carried I132L or D168E substitutions reducing simeprevir median activity by 4.6- and 39-fold, respectively. Six of these eight isolates were from patients achieving sustained virologic response. Baseline NS3 Q80K polymorphism was not observed in the genotype 4-infected patients. Of the 107 simeprevir-treated patients, 37 did not achieve sustained virologic response for any reason. Of the 32 patients who failed treatment and had sequencing information, 28 (88%) had emerging mutations at NS3 positions 80, 122, 155, 156 and/or 168 at time of failure, similar to those in genotype 1. Emerging mutations were mainly D168V and D168E alone or combined with mutations at position 80. In general, isolates obtained at time of failure displayed high-level in vitro resistance to simeprevir (fold change ≥50) in a chimeric replicon assay with a median simeprevir fold change value of 440, consistent with observed mutations. In conclusion, emerging mutations in genotype 4 patients failing simeprevir+peginterferon/ribavirin treatment were similar to those in genotype 1 and conferred high-level resistance to simeprevir. [ABSTRACT FROM AUTHOR]

Pyrenophora semeniperda, an important pathogen in Bromus tectorum seed banks in semi-arid western North America, exhibits >4-fold variation in mycelial growth rate. Host seeds exhibit seasonal changes in dormancy that affect the risk of pathogen-caused mortality. The hypothesis tested is that contrasting seed dormancy phenotypes select for contrasting strategies for increasing pathogen fitness, and that increased fitness on nondormant seeds involves a resource trade-off between toxin production and growth. The strategy for successfully attacking rapidly germinating nondormant seeds at high inoculum loads in autumn involves increased post-infection aggressiveness to prevent seed escape through germination. An earlier study demonstrated that slow-growing strains caused higher mortality than faster-growing strains on nondormant host seeds at high inoculum loads. In this study, production of the toxin cytochalasin B was significantly higher in slower-growing strains, and was induced only in seeds or in seed-constituent-containing media. Its production was reduced in vivo by Bromus tectorum seeds, suggesting direct involvement in pathogenesis on seeds. Fast-growing strains caused significantly higher mortality than slow-growing strains at low inoculum loads on dormant seeds, which apparently have resistance that is overcome at high loads or through rapid mycelial proliferation. In a co-inoculation study, the fast-growing isolate produced 3 × more stromata than the slow-growing isolate on dormant seeds, whereas the slow-growing isolate was twice as successful on nondormant seeds. These results provide evidence that mycelial growth rate variation and associated variation in cytochalasin B production represent a trade-off maintained through temporally varying selection resulting from seasonal variation in host seed dormancy status. [ABSTRACT FROM AUTHOR]

The agricultural landscape of central Europe has changed dramatically in recent decades due to intensified cultivation, bringing many of its characteristic species to the brink of extinction. We investigated whether landscape structure affects the genetic structure and diversity of remnant populations of the two arable plant species Adonis aestivalis and Consolida regalis. We used dominant amplified fragment length polymorphism markers (AFLPs) and compared populations from six regions of 5 km2 in central Germany. These regions represent two different classes of landscape structural complexity: intensively used, homogeneous landscapes (>95% of area covered by arable land with low extent of field margins) or heterogeneous regions (<60% of area covered by arable land with large extent of field margins). Contrary to expectations, within-population diversity levels did not significantly differ between homogeneous and heterogeneous landscapes. No significant isolation-by-distance was found for either species, regardless of landscape structure, and genetic structures may still mirror more continuous conditions before large-scale restructuring commenced in Germany's arable landscapes from the 1950s onwards. These results suggest that current landscape complexity, as such, is not as important for local-level genetic structure for the species studied. Thus, homogenised and intensively used landscapes may also be important for the conservation of arable plant diversity and should not be neglected. [ABSTRACT FROM AUTHOR]

Fanconi anaemia ( FA) is an inherited disease with congenital and developmental abnormalities, cross-linker hypersensitivity and extreme cancer predisposition. With better understanding of the genetic and molecular basis of the disease, and improved clinical management, FA has been transformed from a life-limiting paediatric disease to an uncommon chronic condition that needs lifelong multidisciplinary management, and a paradigm condition for the understanding of the gene-environment interaction in the aetiology of congenital anomalies, haematopoiesis and cancer development. Here we review genetic, molecular and clinical aspects of FA, and discuss current controversies and future prospects. [ABSTRACT FROM AUTHOR]

The OPTIMIZE study demonstrated noninferior efficacy between telaprevir ( TVR) twice daily (bid) vs every 8-h (q8h) administration. This analysis compared the selective pressure of both dosing regimens by characterisation of the hepatitis C virus ( HCV) variants emerging in genotype 1 (G1) HCV-infected patients who did not achieve sustained virological response ( SVR). HCV NS3•4A population sequencing was performed at baseline and time of failure (viral breakthrough, stopping rule or relapse). TVR-resistant variants were classified by fold change in inhibitory concentration ( IC50). Baseline TVR-resistance was low (<5%) and did not preclude achieving SVR in either arm. The proportion of patients with TVR-resistant variants at time of failure was similar in the bid (15%) and q8h (17%) dosing arms. The majority of variants and virological failures occurred in G1a patients, and mutations V36M, R155K and R155T (G1a), and V36A, T54A and A156S (G1b) were significantly enriched in both treatment arms. The number and type of emerging TVR-resistant variants in non- SVR patients were comparable between treatment arms and were consistent with previous observations. No differences in viral resistance profiles were observed between TVR-based treatment arms in non- SVR patients, indicating a similar selective pressure of TVR bid and q8h dosing. [ABSTRACT FROM AUTHOR]

Bromus tectorum (cheatgrass, downy brome) is an important invader in western North America, dominating millions of hectares of former semi-arid shrubland. Stand failure or 'die-off' is relatively common in monocultures of this annual grass. The study reported here investigated whether soil-borne pathogens could be causal agents in die-offs. Soils from two die-off areas and adjacent B. tectorum stands were used in a glasshouse experiment with sterilised and non-sterilised treatments. Soil sterilisation did not increase emergence, which averaged 80% in both die-off and non-die-off soils. Seedling biomass was higher in die-off soils, probably due to increased nitrogen availability. Fusarium was isolated from 80% of killed seeds in non-sterilised soil treatments. In pathogenicity tests with 16 Fusarium isolates, host seeds incubated under water stress (−1.5 MPa for 1 week prior to transfer to free water) suffered over twice the mortality of seeds incubated directly in free water (25-83% with water stress vs. 5-43% without water stress). These results suggest that soil-borne Fusarium could play a role in B. tectorum stand failure in the field, but that low water stress conditions in the glasshouse experiment were not conducive to high levels of disease. Pathogenic Fusarium isolates were obtained from seeds planted in both die-off and non-die-off soils, suggesting that microenvironmental factors that affect levels of water stress might be as important as relative abundance of soil-borne pathogens in mediating spatial patterns of disease incidence in the field. [ABSTRACT FROM AUTHOR]

One recent study indicates a significant association between certain single nucleotide polymorphisms ( SNPs) in the genomic sequence of feline p53 and feline injection-site sarcoma ( FISS). The aim of this study was to investigate the correlation between a specific nucleotide insertion in p53 gene and FISS in a German cat population. Blood samples from 150 German cats were allocated to a control group consisting of 100 healthy cats and a FISS-group consisting of 50 cats with FISS. All blood samples were examined for the presence of the SNP in the p53 gene. Results found the T-insertion at SNP 3 in 20.0% of the cats in the FISS-group and 19.2% of cats in the control-group. No statistically significant difference was observed in allelic distribution between the two groups. Further investigations are necessary to determine the association of SNPs in the feline p53 gene and the occurrence of FISS. [ABSTRACT FROM AUTHOR]

Study C209 evaluated the activity of telaprevir in treatment-naïve patients with genotypes 2 or 3 (G2, G3) hepatitis C virus (HCV) infection. Telaprevir monotherapy showed potent activity against HCV G2, but limited activity against G3. This analysis was performed to characterize HCV viral variants emerging during telaprevir-based treatment of G2/G3 HCV-infected patients. Patients were randomized to receive 2 weeks of treatment with telaprevir (telaprevir monotherapy), telaprevir plus peginterferon alfa-2a and ribavirin (triple therapy), or placebo plus peginterferon alfa-2a and ribavirin (control), followed by 22-24 weeks of peginterferon/ribavirin alone. Viral breakthrough was defined as an increase >1 log10 in HCV RNA from nadir, or HCV RNA >100 IU/mL in patients previously reaching <25 IU/mL. Twenty-three patients (47%) had G2 and 26 (53%) had G3 HCV. Viral breakthrough occurred during the initial 2-week treatment phase in six G2 patients (66.7%; subtypes 2, 2a and 2b) and three G3 patients (37.5%; all subtype 3a), all in the telaprevir monotherapy arm. Four breakthrough patients (three G2, one G3) subsequently achieved sustained virologic response (SVR). In all patients with breakthrough and available sequence data, mutations associated with reduced susceptibility to telaprevir in genotype 1 (G1) HCV were observed. No novel G2/G3-specific mutations were associated with telaprevir resistance. The telaprevir resistance profile appeared consistent across HCV genotypes 1, 2 and 3. Although viral breakthrough with resistance occurred in patients receiving telaprevir monotherapy, half of these patients achieved an SVR upon addition of peginterferon/ribavirin highlighting the importance of combination therapy. [ABSTRACT FROM AUTHOR]

Tigers are globally endangered and continue to decline due to poaching, prey depletion and habitat loss. In Nepal, tiger populations are fragmented and found mainly in four protected areas ( PAs). To establish the use of standard methods, to assess the importance of prey availability and human disturbance on tiger presence and to assess tiger occupancy both inside and outside PAs, we conducted a tiger occupancy survey throughout the Terai Arc Landscape of Nepal. Our model-average estimate of the probability of tiger site occupancy was 0.366 [standard error ( se) = 0.02, a 7% increase from the naive estimate] and the probability of detection estimate was 0.65 ( se = 0.08) per 1 km searched. Modeled tiger site occupancy ranged from 0.04 ( se = 0.05) in areas with a relatively lower prey base and higher human disturbance to 1 ( se = 0 and 0.14) in areas with a higher prey base and lower human disturbance. We estimated tigers occupied just 5049 ( se = 3) km2 (36%) of 13 915 km2 potential tiger habitat (forests and grasslands), and we detected sign in four of five key corridors linking PAs across Nepal and India, respectively indicating significant unoccupied areas likely suitable for tigers and substantial potential for tiger dispersal. To increase tiger populations and to promote long-term persistence in Nepal, otherwise suitable areas should be managed to increase prey and minimize human disturbance especially in critical corridors linking core tiger populations. [ABSTRACT FROM AUTHOR]

Rye (Secale cereale L.) is a frequently used winter cover crop in many agronomic production systems in the United States. Our objective was to determine whether incorporating rye into soil while still green results in greater suppression of root-knot nematodes (Meloidogyne spp.) and Palmer amaranth (Amaranthus palmeri S. Wats.) compared to conventional cover crop management. Two similar experiments were conducted: one with peanut (Arachis hypogaea L.) and the other with cotton (Gossypium hirsutum L.). Both experiments were a split-plot design with tillage as the main plot (conventional, green manure, and strip) and cover crop as the subplot. The cover crop treatments were a weedy fallow and the rye cultivars Wrens Abruzzi, Wheeler, Oklon, and Elbon. Wrens Abruzzi produced the greatest amount of biomass, Oklon and Elbon intermediate, and Wheeler the least. Where there was substantial soil disturbance (e.g., conventional tillage and green manure), Palmer amaranth densities were low and not influenced by cover crop. In the strip tillage plots, however, all of the rye cultivars, except Wheeler, reduced establishment of the weed compared to winter fallow. Root galling from nematodes on cotton and peanut was influenced by tillage, but not by rye cover crop. Gall indices on cotton were greater in conventional tillage than in either strip tillage or green manure plots; whereas on peanut, they were greater in the strip tillage than in the conventional tillage or green manure plots. Neither tillage nor cover crop influenced yield except in 2008 in peanut, where yield was lower in strip tillage than in conventional or green manure plots. [ABSTRACT FROM AUTHOR]

Hepatic failure is one of the more common complications in foals requiring blood transfusion to treat neonatal isoerythrolysis. Iron intoxication is likely the cause of hepatic injury. To determine the effects of deferoxamine on iron elimination in normal foals. Thirteen neonatal foals. Randomized-controlled trial. At 1-3 days of age, foals received either 3 L of washed packed dam's red blood cells (RBC) or 3 L of saline IV once. Foals were treated with deferoxamine (1 g) or saline (5 mL) SC twice daily for 14 days. Foals were randomly assigned to 1 of 3 groups: RBC/deferoxamine (deferoxamine), RBC/saline (placebo), or saline/saline (control). Blood and urine samples and liver biopsy specimens were collected for measurement of hematological, biochemical, and iron metabolism variables. There was a significant ( P < .05) increase in hematocrit, RBC count, and hemoglobin in the groups transfused with packed RBC as compared with controls at all times. Biochemical variables and liver biopsy scores were not significantly different between groups at any time. Urine iron concentrations and fractional excretion of iron were significantly higher in deferoxamine treated foals. By 14 days after transfusion, liver iron concentrations in foals treated with deferoxamine (79.9 ± 30.9 ppm) were significantly lower than that of foals receiving placebo (145 ± 53.0 ppm) and similar to that of controls (44.8 ± 4.09 ppm). Deferoxamine enhances urinary iron elimination and decreases hepatic iron accumulation after blood transfusion in foals. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration ( MIC) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1–2 days-of-age and 4–5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six additional foals between 1 and 5 days of age at a dose of 5 mg/kg q 12 h. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur-related metabolites were measured in plasma, synovial fluid, urine, and CSF by use of UPLC-MS/MS. A microbiologic assay was used to measure ceftiofur activity for a subset of plasma samples. Following i.v. administration of ceftiofur at a dose of 5 mg/kg to 1–2 day-old foals, DCA had a t½ of 7.8 ± 0.1 h, a body clearance of 74.4 ± 8.4 mL/h/kg, and an apparent volume of distribution of 0.83 ± 0.09 L/kg. After multiple i.v. doses at 5 mg/kg, DCA concentrations in CSF were significantly lower than concurrent plasma concentrations. Ceftiofur activity using a microbiologic assay significantly underestimated plasma concentrations of DCA. The MIC of ceftiofur required to inhibit growth of 90% of isolates of Escherichia coli, Pasteurella spp, Klebsiella spp, and β-hemolytic streptococci was <0.5 μg/mL. Intravenous administration of ceftiofur sodium at the rate of 5 mg/kg every 12 h would provide sufficient coverage for the treatment of susceptible bacterial isolates. [ABSTRACT FROM AUTHOR]

Objective GH acts through the GH receptor (GHR). The GHR gene contains a genetic polymorphism caused by a deletion of exon 3 ( d3), with high frequency in the normal population. There is a continuing controversy whether the presence or absence of the exon 3 deletion ( d3+ vs. d3–) affects the effect of GH in human growth. Design, patients and measurements For 144 patients with idiopathic isolated GH deficiency (IGHD, n = 72) or multiple pituitary hormone deficiency (MPHD, n = 72), amplification of the region around exon 3 of the GHR gene was performed. Clinical data and response to GH treatment were compared between GHR d3+and d3– IGHD and MPHD patients born either small for gestational age (SGA) or appropriate for gestational age (AGA). Results IGHD patients born SGA had a significantly higher d3+frequency (82%) than IGHD patients born AGA (35%, P = 0·006). Within the group of IGHD patients born SGA, d3– patients showed a slightly better spontaneous catch up growth before start of GH treatment than d3+ patients (1·1 ± 1·1 SD vs. 0·6 ± 1·1 SDS, P = 0·040) There was no difference in patients first year's response to GH treatment between GHR d3+ and d3– patients. Conclusions In IGHD and MPHD patients, response to GH treatment was independent of GHR genotype. GHR- d3 was significantly more frequent among IGHD patients born SGA. As we are the third to report an association between birth size and GHR d3 status, it is conceivable that the GHR- d3 might affect prenatal growth in IGHD patients by a yet unknown mechanism. [ABSTRACT FROM AUTHOR]

Severe septic and cardiogenic shock is associated with a high mortality in neonates, children and adolescents. Common therapies include the administration of fluids and the use of conventional inotropes. However, in severe forms of shock, cardio-circulatory failure may be secondary to profound vasoparalysis and unresponsive to conventional therapies. We reviewed the literature on the use of arginine-vasopressin (AVP) and terlipressin (TP) as a rescue therapy in neonates, children and adolescents with catecholamine-refractory shock or cardio-circulatory arrest. We identified 17 reports (11 case series, 6 case reports) on a total of 109 patients. Only two studies were prospective. The age of treated patients ranged from extremely low birth weight infants of 23 weeks' gestation to a 19-year-old adolescent. The most common indication for either drug was catecholamine-refractory septic shock (nine reports). Commonly reported responses following AVP/TP administration were a rapid increase in systemic arterial blood pressure, an increase in urine output, and a decrease in serum lactate. In most reports, AVP and TP had a significant impact on the required dose of inotropes which could be reduced. Despite the use of AVP/TP, mortality was high (52/109). In view of the limited number of paediatric patients treated with AVP/TP, no definite recommendations on their use in children with severe forms of cardio-circulatory failure can be issued. There is a need for larger prospective trials assessing the efficacy and safety profiles of these drugs in a defined setting. Until more data are available, and taking into consideration the detrimental impact catecholamine-refractory shock has on children, the use of AVP/TP as a rescue therapy should be considered on an individual basis. [ABSTRACT FROM AUTHOR]

Purpose Population-based data about patterns and prevalence of antidepressant drug use is limited in Europe and presently unavailable for Germany. Therefore, we have identified patterns and prevalence of antidepressant use among outpatients on a population-based scale in the German state of Baden-Wuerttemberg. Methods We conducted a historical cohort study using a computerised prescription database referring to all members of the major German public health insurance company AOK. We assessed the prevalence of antidepressant drug use over a 3-year period, calculated the number of prescription items purchased per patient and compared first-line and second-line treatments. Results The 1-year prevalence of antidepressant drug use among more than 4 000 000 health insurance members was 7.4% (male: 4.3%; female: 10.2%). Importantly, almost 40% of the patients received only a single prescription item from 2000 to 2002. Though the use of serotonin-reuptake inhibitors (SSRIs) markedly increased by about 65% within the study period, these are primarily used as second-line drugs and still much less frequently than St. John's wort or tricyclic antidepressants such as amitryptiline or doxepin. Conclusions The prevalence of antidepressant drug use is higher than previously reported for other European countries. The preferred use of St. John's wort and tricyclics over SSRIs and other modern-type antidepressants in Germany is quite unique in Europe and different from the US. The identified drug use pattern leaves a major room for improvement in view of the numerous single prescription items purchased. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Bromus tectorum is a dominant winter annual weed in cold deserts of western North America. We followed patterns of seed carry-over and abundance of the pathogen Pyrenophora semeniperda over 5 years at B. tectorum-dominated shadscale ( Atriplex confertifolia) and sagebrush ( Artemisia tridentata) sites in southern Idaho. We hypothesised that more seeds could potentially carry over at the drier shadscale site because of minimal autumn precipitation, but that P. semeniperda, a pathogen that primarily kills dormant seeds, would have more impact at the drier site, where a higher density of dormant seeds would likely be present in the early spring seedbank. Successful first-year seed carry-over was higher in years with below-average autumn precipitation. It was lower at the shadscale site than at the sagebrush site (9% vs.16%). The number of seeds killed during incubation by P. semeniperda averaged three times higher at the drier site and the number of field-killed seeds averaged almost five times higher. This suggests that pathogen-related mortality caused the greater decrease in seed carry-over at the drier site. Mortality risk increased dramatically with seed age. This climate–pathogen interaction apparently limits B. tectorum seedbank carry-over in cold deserts to 3 years or less. Pyrenophora semeniperda shows potential as a biocontrol agent for B. tectorum in these habitats. [ABSTRACT FROM AUTHOR]

1. Leaf-cutting ants (LCA) are highly polyphagous but at the same time highly selective dominant herbivores of neotropical rainforests. While a whole range of leaf properties has been identified to influence interspecific host choice, the mechanisms underlying intraspecific and intra-individual herbivory patterns remain obscure. Here, we evaluate the plant-stress hypothesis by analysing whether and how drought stress of food plants positively affects LCA food plant selection. 2. In bioassays with whole plants of Piper marginatum, Atta colombica workers harvested more than twice the leaf area of stressed than of vigorous control plants. Within individual plants, the attractiveness of a given leaf increased with its stress level. 3. Drought stress induced an accumulation of proline and non-structural carbohydrates in the plant tissue by a factor of 3·5 and 2, respectively, accompanied by a decrease in the leaf water content of about 35%. Moreover, samples taken from preferred leaves within a plant contained more osmolytes than those representing the whole plant. 4. Ants were shown to detect and prefer these osmolytes in bioassays conducted with leaf discs that had been experimentally enriched with proline and/or sucrose. We therefore propose a mechanism that links the preference of LCA to drought stress via the osmolyte concentrations within the leaves. 5. Our results support the plant-stress hypothesis, confirming that stressed plants and plant parts are more attractive to LCA. This may account for intraspecific and intra-individual herbivory patterns of LCA, thus influencing populations of host species through the discrimination of drought-sensitive individuals. [ABSTRACT FROM AUTHOR]

There is an ongoing debate as to whether propofol exhibits pro- or anticonvulsant effects, and whether it should be used in patients with epilepsy. We prospectively assessed the occurrence of seizure-like phenomena and the effects of intravenous propofol on the electroencephalogram (EEG) in 25 children with epilepsy (mean (SD) age: 101 (49) months) and 25 children with learning difficulties (mean (SD) age: 52 (40) months) undergoing elective sedation for MRI studies of the brain. No child demonstrated seizure-like phenomena of epileptic origin during and after propofol sedation. Immediately after stopping propofol, characteristic EEG changes in the epilepsy group consisted of increased beta wave activity (23/25 children), and suppression of pre-existing theta rhythms (11/16 children). In addition, 16 of 18 children with epilepsy and documented EEG seizure activity demonstrated suppression of spike-wave patterns after propofol sedation. In all 25 children with learning difficulties an increase in beta wave activity was seen. Suppression of theta rhythms occurred in 11 of 12 children at the end of the MRI study. In no child of either group was a primary occurrence or an increase in spike-wave patterns seen following propofol administration. The occurrence of beta wave activity (children with learning difficulties and epilepsy group) and suppression of spike-wave patterns (epilepsy group) were transient, and disappeared after 4 h. This study demonstrates characteristic, time-dependent EEG patterns induced by propofol in children with epilepsy and learning difficulties. Our data support the concept of propofol being a sedative-hypnotic agent with anticonvulsant properties as shown by depression of spike-wave patterns in children with epilepsy and by the absence of seizure-like phenomena of epileptic origin. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B progresses to cirrhosis in the majority of immunosuppressed patients. The outcome of long-term antiviral therapy in HBV-infected organ transplant recipients is unknown. In 1996, we included 20 heart transplant (HT) recipients in a pilot trial to treat chronic hepatitis B with famciclovir. At that time, bridging fibrosis or cirrhosis was evident in 15 individuals (75%). From 1998 onwards, patients were switched to lamivudine in case of primary or secondary virological nonresponse to famciclovir. Adefovir or tenofovir became available at our centre for HT recipients in 2002. After 103 months, one patient was still on famciclovir showing a complete virological response. Sixteen patients were switched to lamivudine after 0.5–4 years of famciclovir therapy. Six of those showed a long-term response to lamivudine therapy lasting for up to 7 years. Lamivudine resistance developed in the remaining 10 patients (63%), in 4 of them successful rescue therapy (adefovir n = 3, tenofovir n = 1) could be initiated. Only one hepatocellular carcinoma developed, which was successfully treated by locoregional ablative therapy. Nine patients died (45%), with lamivudine-resistance-related liver failure as the cause of death in five cases. Significant improvement of Ishak fibrosis scores could be demonstrated in six of the seven patients with more than two sequential liver biopsies available. Long-term antiviral therapy of chronic hepatitis B can lead to regression of liver cirrhosis in patients after organ transplantation, unless viral resistance occurs. This study demonstrates the urgent need for further antivirals to overcome antiviral resistance. [ABSTRACT FROM AUTHOR]

Chlorophyll (Chl) and epidermal polyphenol (EPhen) contents were estimated in vivo using two optical leaf-clips, SPAD-502 and Dualex, respectively. The area-based measurements were transformed into mass-based data by taking into account the leaf dry mass per area (LMA). Measurements were performed on forest trees and on saplings grown under controlled conditions. While LMA increased with irradiance along a vertical transect in a beech canopy or in saplings grown under different and increasing irradiance levels, mass-based EPhen (EPhenm) increased, whereas mass-based Chl (Chlm) decreased. This was a signature of a gradual switch of investment from protein into polyphenol production. A similar signature was obtained in saplings grown on nitrogen-deficient soil with respect to fertilized controls. However, nitrogen effects remained moderate compared to irradiance-induced effects. EPhenm and Chlm both declined with plant ageing-induced increases in LMA, under all tested growth conditions. This was a signature of an accumulation of dry matter that diluted Chl and EPhen. The described competition between Chl and EPhen in leaves fits well with the predictions of the Protein Competition Model (PCM), that is, that the total leaf mass-based polyphenols content (Phent) is controlled by the competition between protein and polyphenol biosynthetic pathways and its metabolic regulation. [ABSTRACT FROM AUTHOR]

This prospective, clinical trial evaluated the effects of short-term propofol administration on triglyceride levels and serum pancreatic enzymes in children undergoing sedation for magnetic resonance imaging. Laboratory parameters of 40 children, mean age (SD; range) 67 (66; 4–178) months undergoing short-term sedation were assessed before and 4 h after having received propofol. Mean (SD) propofol loading dose was 2.2 (1.1) mg.kg−1 followed by continuous propofol infusion of 6.9 (0.9) mg.kg−1.h−1. Serum lipase levels (p = 0.035) and serum triglyceride levels (p = 0.003) were raised significantly after propofol administration but remained within normal limits. No significant changes in serum pancreatic-amylase levels were seen (p = 0.127). In two (5%) children, pancreatic enzymes and in four (10%) children triglyceride levels were raised above normal limits; however, no child showed clinical symptoms of pancreatitis. We conclude that even short-term propofol administration with standard doses of propofol may have a significant effect on serum triglyceride and pancreatic enzyme levels in children. [ABSTRACT FROM AUTHOR]

Metoprolol, a widely prescribedβ-adrenergic receptor blocker, has occasionally been associated with a diversity of cutaneous reactions. We present a 79-year-old male patient with erosive lichen planus (LP) on the feet and hands who was successfully treated with topical tacrolimus. Six months after the lesions had been cured the patient received theβ-receptor blocker metoprolol for the treatment of hypertonus. Within only 2 weeks of metoprolol intake the erosive lesions on the palms and feet recurred. After discontinuation of the drug and repetitive topical treatment with tacrolimus a complete remission of the lesions could be achieved. The recurrence of erosive LP probably secondary to metoprolol and the therapeutic success of topical tacrolimus in the treatment of LP are discussed. [ABSTRACT FROM AUTHOR]

Zaidi SHE, Peltekova V, Meyer S, Lindinger A, Paterson AD, Tsui L-C, Faiyaz-Ul-Haque M, Teebi AS. A family exhibiting arterial tortuosity syndrome displays homozygosity for markers in the arterial tortuosity locus at chromosome 20q13.Arterial tortuosity associated with hyperextensible skin and hypermobility of joints, features that are characteristics of Ehlers–Danlos syndrome (EDS), has been described in several families. An arterial tortuosity locus has recently been mapped to chromosome 20q13. Here, we report a consanguineous Kurdish family in which an affected child manifested elongation and severe tortuosity of the aorta, carotid, and other arteries. Additional clinical symptoms include loose skin, hypermobile joints, hernias, and facial features that resemble EDS individuals. To examine whether the arterial tortuosity locus was involved in this child, homozygosity analysis was performed using microsatellite markers on 20q13. The affected child was found homozygous, whereas the unaffected parents and three siblings were heterozygous. Additional typing defined the genomic interval to a 37-cmregion within which the arterial tortuosity locus is located. Three functional candidate genes (B4GALT5,KCNB1, andPTGIS) were sequenced. No mutations were discovered in the coding regions of these three genes and the promoter regions ofB4GALT5andKCNB1genes. Moreover, the B4GALT5 mRNA expression was unaltered in patient-derived lymphoblastoid cells. In thePTGISgene promoter, the affected child was homozygous for eight variable number of tandem repeats, while parents and unaffected siblings carried six repeats. [ABSTRACT FROM AUTHOR]

Abstract The process of receptor-mediated uptake of hexamerin storage proteins from insect haemolymph by fat body cells is a unique feature of the class Insecta . We identified the binding domains of the hexamerin receptor and the hexamerin ligand arylphorin in the blowfly, by means of the yeast-two-hybrid-system. The receptor-binding domain of arylphorin was located within domain 3 of the arylphorin monomer. The ligand-binding domain of the hexamerin receptor was mapped to the extreme N-terminus of the receptor. The binding domains identified exhibit no similarity to any functional protein domains known to date. Additionally, we identified two previously unknown protein-interactors of the hexamerin receptor. The results of this study provide further insights regarding the mechanism of the receptor-mediated endocytosis of storage proteins in insects. [ABSTRACT FROM AUTHOR]

Tie-2, a tyrosine kinase receptor, is essential for vascular integrity by regulating cellular adhesion between pericytes and endothelial cells. The aim of this study was to identify sites of expression of Tie-2 other than the vasculature. Tie-2 expression was first detected in human colon by Western blotting and reverse-transcription-polymerase chain reaction (RT-PCR) in tissue extracts. The presence of the Tie-2 mRNA and protein was detected by immunohistochemistry and in situ hybridization in cells of the colon myenteric and submucosal plexus, in both neuronal and Schwann cells. Tie-2 protein was also found in the nervous system of the female urogenital tract. In the human sciatic nerve and schwannoma, RT-PCR, Western blotting and immunohistochemistry analysis further confirmed the presence of Tie-2 mRNA and protein in non-autonomic peripheral nervous tissue. In conclusion, using several approaches and tissues we have demonstrated the presence of Tie-2 in human peripheral and autonomic nervous tissue, suggesting a role for Tie-2 in neural tissue. Thus, attempts to disrupt the tumour vessels by manipulation of the Tie-2 system in tumours may result in side-effects in peripheral nerves. [ABSTRACT FROM AUTHOR]

Abstract In this study a method was designed to assess non-destructively the type of UV-screening compounds present in the leaf epidermis. The method is based on the recording and calculation of the ratio of UV-excitation spectra of chlorophyll fluorescence (FER) from the adaxial and abaxial sides of bifacial leaves, or from older and younger segments of monocotyledonous leaves. The logarithm of this ratio (logFER) matched the absorption spectrum of the UV-absorbers present in the leaf, as confirmed by its overlap with the absorption spectrum of the methanolic extract of the leaf or of the isolated epidermis. By using the logFER approach, it was possible to demonstrate that the concentration but not the classes of compounds present in the epidermis that are responsible for UV-screening is affected by the side and the age of the leaves. In contrast, measurements from the leaves of seven dicots and one monocot indicated large difference in the classes of these compounds between species. Finally, it was shown that the logFER in the UV is independent of the emission wavelength, and that the method can be used for quantitative measurements. This method expands to the spectral domain the use of ChlF for the estimation of the leaf epidermal transmittance. [ABSTRACT FROM AUTHOR]

Population changes in long-eared owls Asio otus, polecats Mustela putorius, red foxes Vulpes vulpes, stone martens Martes foina and badgers Meles meles were monitored during a water vole Arvicola terrestris scherman cycle in western Switzerland. Long-eared owls confirmed their status of highly mobile specialist predators in responding strongly and without time lag to water vole population changes. Even though polecats are considered generalists, they exhibited also a strong response to water vole fluctuations. Their numbers tracked water vole densities with a 1-yr time lag. Marked population changes were also recorded in red foxes and stone martens, but these changes were not related to water vole densities. Lastly, badgers did not show any significant population changes during the water vole cycle. We discuss the possible reasons for these differences and conclude that multi-factorial approach is clearly required to understand population processes in predator-prey systems. [ABSTRACT FROM AUTHOR]

Abstract We cloned and sequenced a full length cDNA coding for [Arg7]-corazonin in the greater wax moth Galleria mellonella. The deduced corazonin preprohormone consists of a nineteen amino acid signal peptide, the actual eleven amino acid corazonin sequence, followed by a Gly serving for amidation, a Lys-Arg processing site and an eighty amino acid corazonin precursor-related peptide. The data confirm the phylogenetic conservation of the actual corazonin sequence. The signal peptide and the precursor-related peptide exhibit a similar spacing of a few amino acids as detected in the corazonin preprohormone of Drosophila melanogaster. Northern blots and in situ hybridization experiments revealed that the G. mellonella corazonin gene is tissue-specifically expressed in four pairs of lateral neurosecretory cells in the brains of penultimate and last instar larvae, as well as of pupae and adults. No corazonin mRNA was detected in other cells of the nervous system, fat body, gut, and several other organs. [ABSTRACT FROM AUTHOR]